Local anaesthetics

Question 1

What is an AP?

Answer 1

1. When stimulus reaches threshold depolarisation, an AP is generated, All or nothing
2. Very short lived
3. After repolarisation, a hyperpolarisation period follws–>Refractory period

Question 2

What is a refractory period?

Answer 2

• A period due to inactivation of voltage-gated Na+ channels

Question 3

How does information flow through APs?

Answer 3

• AP encode info by Frequency not amplitude
• Upper freq limit imposed by refractory period

Question 4

How do LAs function?

Answer 4

• Inhibit VGSC (by binding to intracellular side)–> Block conduction of APs—-> BLock pain

Question 5

What are LAs?

Answer 5

• Weak bases that need to cross plasma membrane in an un-ionised form but bind to VGSC in ionised form

Question 6

What are some examples of LAs?

Answer 6

• Esters:
• Metabolised by non-specific esterases in the plasma and tissues
• Amides:
• More-stable, with longer half-lives, and metabolised by liver amidases

Question 7

Explain differential sensitivity to LAs.

Answer 7

• Nerve bundles consist of multiple fibre types
• Myelinated and thicker axons are more difficult for LAs to penetrate than thin, unmyelinated.

Question 8

What are unwanted effects of LAs?

Answer 8

• Unwanted effects are due mainly to escape of LA into systemic circulation
• Main unwanted effects are:
  1. CNS effects
  2. CVS effects
  3. Hypersensitivity reactions

Question 9

What are the unwanted CNS effects of LAs?

Answer 9

• Agitation
• Confusion
• Tremors
• Respiratory depression

Question 10

What are the unwanted CVS effects of LAs?

Answer 10

1. Myocardial depression
2. Vasodilation
3. Leads to fall in BP